DESCRIPTION (Applicant's abstract): The literature indicate that physically active organisms are less susceptible to the deleterious consequences of stress on illness and immune function. Using an established animal model of stress, my laboratory has investigated the effect of acute stressor exposure on the development of a specific antibody response to a benign protein, keyhole limpet hemocyanin (KLH) in physically active versus sedentary rats. Measurement of specific antibody levels in the blood after challenge with KLH provides an excellent measure of the in vivo immune response, and a reduction in the specific antibody response to a bacteria, virus or soluble toxin, could render the organism more susceptible to disease caused by that pathogen. Sedentary rats that are immunized with KLH, and exposed to a single session of tail shock stress, have a reduction in the antibody response to KLH (anti-KLH Ig). In contrast, rats that are allowed to live with a running wheel before exposure to an acute stressor, do not suffer the immunologically deleterious consequences of stress. The central theme of this proposal is to determine the immune-neuroendocrine-brain mechanism(s) of the stress-buffering effect of physical activity. Preliminary data suggest that physical activity modulates the brain and neuroendocrine responses to stressor exposure. Compared to sedentary stressed rats, physically active rats exposed to tail shock stress have a smaller increase in c-Fos immunoreactivity (neuronal activation marker) in several stress reactive brain areas that are important for activation of sympathetic descending pathways. These changes may be responsible for the reduction in stress-induced sympathetic nervous system output (plasma and splenic norepinephrine (NE)) found in physically active versus sedentary animals. Importantly, there is evidence that exposure to stress levels of NE elevates nitric oxide (NO) which leads to a reduction in anti-KLH Ig. Blockade of stress-induced sympathetic output prevents these effects. It is reasonable to hypothesize, therefore, that physically active rats are resistant to the negative effects of stress on immune function because they have a reduction in sympathetic nervous system output leading to a reduction in immunosuppressive NO, and prevention of suppressed anti-KLH Ig.